Does having marked hyperglycemia increase stroke bleeding risk with bridging therapy?

Bridging therapy combines intravenous clot-dissolving medication (alteplase) with mechanical clot removal (endovascular thrombectomy, EVT). Direct EVT skips the medication. For people with very high blood sugar (marked hyperglycemia) at the time of stroke, bridging therapy appears to raise the risk of a serious type of bleeding called parenchymal hematoma (PH). A 2026 analysis of the DIRECT-MT trial found that in patients with glucose levels above 11.1 mmol/L (about 200 mg/dL), bridging therapy was linked to a nearly 5-fold higher odds of PH compared to direct EVT ⁶⁸.

What the research says

A post-hoc analysis of the DIRECT-MT trial, which included 627 patients with large-vessel occlusion stroke, examined how admission blood glucose affected bleeding risk with bridging therapy versus direct EVT ⁶⁸. Overall, higher glucose was tied to greater odds of any hemorrhagic transformation (adjusted OR 1.168 per 1 mmol/L increase) ⁶⁸. The key finding was a significant interaction: at glucose levels above 11.1 mmol/L, bridging therapy was associated with a much higher risk of parenchymal hematoma (OR 4.84; 95% CI 1.34-21.95) ⁶⁸. In the same high-glucose subgroup, there was no excess bleeding risk with direct EVT ⁶⁸. This suggests that marked hyperglycemia specifically amplifies the hemorrhagic danger of adding intravenous alteplase before mechanical clot removal. Older animal research also supports that hyperglycemia worsens vascular damage and increases hemorrhagic transformation after cerebral ischemia ¹⁰. While the DIRECT-MT analysis is the most direct human evidence, it is a post-hoc analysis, meaning the finding needs confirmation in dedicated trials.

What to ask your doctor

• If my blood sugar is very high at the time of stroke, is bridging therapy or direct EVT safer for me?
• What glucose level would be considered 'marked hyperglycemia' in my case, and how is it measured?
• Are there other factors (like kidney function or medication timing) that might further increase bleeding risk with bridging therapy?
• Should my blood sugar be lowered before or during stroke treatment to reduce bleeding risk?
• What is the evidence behind the choice of bridging therapy versus direct EVT for patients with high blood sugar?